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SYNGAP1-related disorders describe a group of disorders caused by pathogenic mutations in the SYNGAP1 gene. This gene is responsible for the production of SynGap, which is a protein essential for healthy brain function and development. The protein is located in the connections between nerve cells (neurons) that carry messages for learning and memory. Without adequate levels of the SynGap protein, individuals experience profound delays in early childhood, presenting as epilepsy (seizures), intellectual disability and/or autism spectrum disorder, and other behavioral, social, and sensory issues.
Symptoms of SYNGAP1-related disorders are frequently observed in three main categories: (1) learning and speech, (2) behavior, (3) motor skills and movement. These symptoms range from mild to severe and not every patient will have an identical set of symptoms.
Based on current data, SYNGAP1-related disorders are equally prevalent in both sexes and all ethnic groups. The first case of the disorder was diagnosed in 2009, and there are now approximately 985 people diagnosed worldwide [x]. With advancing science, researchers expect the number of identified cases to steadily increase.
SYNGAP1 follows an autosomal dominant inheritance pattern—meaning one copy of the altered gene can cause the disease. Most cases of SYNGAP1 occur in individuals who have no family history of the disorder. Mutations that are not from either parent are de novo and develop spontaneously.
Diagnosing SYNGAP1 begins with a physical examination. Physicians look for key features and secondary diagnoses commonly associated with SYNGAP1. This includes children with global developmental delay, intellectual disability, autism, epilepsy, or acquired microcephaly. Together, these symptoms warrant genetic sequencing to screen for causative genes. There is more than one gene related to the above characteristics, which is why genetic testing must specifically include the SYNGAP1 gene.
Aside from genetic testing, an electroencephalogram (EEG) to measure abnormal brain activity is helpful for determining if seizure activity is present. However, magnetic resonance imaging (MRI) of brain structure is typically normal in SYNGAP1-related disorders, with abnormal imaging suggestive of alternative diagnoses.
There is no cure for SYNGAP1-related disorders. However, it is possible to treat some of the symptoms.
Medications can lessen the frequency of seizures in those with epilepsy. When medication is ineffective, implantable devices like vagus nerve stimulation (VNS) or responsive neurostimulation (RNS) may control seizures.
Cognitive and developmental delays, as well as behavioral changes, are managed during early developmental interventions such as occupational, speech, and physical therapy. Occupational therapy teaches patients skills for completing day-to-day tasks as independently as possible. Speech therapy is crucial, especially in those with oral motor dysfunction, to encourage speech production and overcome feeding difficulties. Physical therapy creates a customized exercise plan which allows those with SYNGAP1-related disorders to improve hypotonia (i.e., low muscle tone) and prevent extensive weakness.
Some children experience developmental regression and forget skills they have already learned; It is therefore recommended that patients are consistent with their therapies to prevent regression.
What is the life expectancy for those with SYNGAP1-related disorders? With so few patients diagnosed, life expectancy remains unknown. Multiple adult patients aged 31 to 65 are noted in medical literature [x], and when premature death does occur, it is typically due to complications from epileptic seizures (i.e., choking, aspiration). Fortunately, if seizures are well controlled and with consistent early interventions, people with SYNGAP1-related disorders are able to learn and thrive.
To learn more about SYNGAP1-related disorders, visit the SynGap Research Fund.
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